Abstract
Background
Dopamine (DA) is hypothesized to modulate anxiety-like behavior, although the precise
role of DA in anxiety behaviors and the complete anxiety network in the brain have
yet to be elucidated. Recent data indicate that dopaminergic projections from the
ventral tegmental area (VTA) innervate the interpeduncular nucleus (IPN), but how
the IPN responds to DA and what role this circuit plays in anxiety-like behavior are
unknown.
Methods
We expressed a genetically encoded G protein–coupled receptor activation–based DA
sensor in mouse midbrain to detect DA in IPN slices using fluorescence imaging combined
with pharmacology. Next, we selectively inhibited or activated VTA→IPN DAergic inputs
via optogenetics during anxiety-like behavior. We used a biophysical approach to characterize
DA effects on neural IPN circuits. Site-directed pharmacology was used to test if
DA receptors in the IPN can regulate anxiety-like behavior.
Results
DA was detected in mouse IPN slices. Silencing/activating VTA→IPN DAergic inputs oppositely
modulated anxiety-like behavior. Two neuronal populations in the ventral IPN (vIPN)
responded to DA via D1 receptors (D1Rs). vIPN neurons were controlled by a small population of D1R neurons
in the caudal IPN that directly respond to VTA DAergic terminal stimulation and innervate
the vIPN. IPN infusion of a D1R agonist and antagonist bidirectionally controlled
anxiety-like behavior.
Conclusions
VTA DA engages D1R-expressing neurons in the caudal IPN that innervate vIPN, thereby
amplifying the VTA DA signal to modulate anxiety-like behavior. These data identify
a DAergic circuit that mediates anxiety-like behavior through unique IPN microcircuitry.
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Article info
Publication history
Published online: June 29, 2020
Accepted:
June 16,
2020
Received in revised form:
June 15,
2020
Received:
March 3,
2020
Identification
Copyright
© 2020 Society of Biological Psychiatry.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Dopamine Release in the Midbrain Promotes AnxietyBiological PsychiatryVol. 88Issue 11
- PreviewThe mesolimbic dopamine system is at the center of information processing and sends projections throughout the brain that have been linked to reward, motivation, salience, novelty, and the regulation of affective states (1). This system has been a major focus of psychiatric disease research given the critical role it plays in mood disorders—including anxiety disorders, where its dysregulation has been linked to the expression of negative affective states in human and animal models (2,3). Therefore, a significant effort has focused on understanding how the dopamine system encodes information and how dopamine projections balance competing information to drive the expression of adaptive and maladaptive behaviors.
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